Midostaurin for FLT3-Mutated AML, 10 Years Later

AML treatment has evolved from relying solely on standard chemotherapy to incorporating more personalized, targeted therapies based on specific AML subtypes.

One of the first clinical trials to evaluate a targeted therapy in combination with chemotherapy for AML was the RATIFY study. This trial assessed the FLT3 inhibitor midostaurin (Rydapt, Novartis) alongside chemotherapy for newly diagnosed patients with FLT3-mutated acute myeloid leukemia (AML). The positive results of the RATIFY trial led to the FDA's approval of this treatment combination in 2017.

A key question specialists sought to answer was: Do AML patients continue to benefit from midostaurin a decade after treatment?

Richard M. Stone, MD, of Dana-Farber Cancer Institute, led the research investigating this question, and the findings were presented at the 2024 ASH conference. 

Read about this study below!

10-Year Results of Midostaurin for FLT3-Mutated AML

In the RATIFY trial, 717 patients with FLT3-mutated AML received either midostaurin or a placebo alongside standard intensive chemotherapy. After initial treatment, they underwent maintenance therapy with midostaurin or placebo for one year. If eligible, they proceeded to an allogeneic stem cell transplant.

At the 10-Year Follow-up:

• Overall survival: Among the 420 patients who achieved complete remission (full reduction of AML cells) within 60 days post-treatment, overall survival was higher in the midostaurin group (43.7%) compared to the placebo group (38.6%).
• Differences between men and women: Men who took midostaurin experienced a greater overall survival benefit than women.
• Impact of stem cell transplant:
  • Of the 414 patients who underwent an allogeneic stem cell transplant, 56% were alive at the 10-year mark. This was significantly higher than the 35.8% survival rate among those who did not receive a transplant.
  • Among patients who achieved complete remission and could proceed to receive a transplant, 61.5% had taken midostaurin, compared to 49% who had received the placebo.
  • For those who did not receive a transplant, 51.8% of surviving patients had taken midostaurin, compared to 48.0% who had received the placebo.
• Relapse risk:
  • Among patients who achieved complete remission and received maintenance therapy with midostaurin, those with favorable or intermediate-risk AML had a lower chance of relapse. High-risk patients did not experience this same benefit. 

Conclusion

People with FLT3-mutated AML who received midostaurin in combination with chemotherapy saw an increased chance of remaining free from cancer-related complications over time compared to patients in the control group. 

While overall survival was not significantly increased—likely due to aging—one key finding was that patients with favorable or intermediate-risk AML who achieved complete remission and received midostaurin as maintenance therapy had a reduced risk of relapsing. 

To learn more about FLT3 inhibitors as maintenance therapy for AML, read the following article: FLT3 Inhibitors Gilteritinib and Quizartinib as AML Maintenance Therapies

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Sources: 

• 10 Year Follow-up of CALGB 10603/Ratify: Midostaurin Versus Placebo Plus Intensive Chemotherapy in Newly Diagnosed FLT3 Mutant Acute Myeloid Leukemia Patients Aged 18-60 Years
• Acute Myeloid Leukemias: Commercially Available Therapies: Impact of Molecularly-Targeted Agents in AML
• Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia